The proposed work concerns studies on the control of purine biosynthesis in liver and cultured human fibroblasts in order to elucidate the ways in which a defective regulation of purine metabolism leads to gout. The approach is to study individual components of the purine synthesizing and interconverting processes in liver of rats under dietary conditions known to have markedly different rates of purine biosynthesis. This approach is being supplemented with studies on cultured human fibroblasts from normal as well as patients with clinical gout. Isolated rat liver cells and cultured human fibroblasts are being incubated in nutritionally adequate media supplemented with various purines and C14-glycine in an attempt to correlate enzyme activities, de novo purine biosynthesis, purine nucleotide pool sizes and purine excretion patterns in these cells.